The major objective of this research proposal is to study the basic biological processes involved in the regulation and control of the blood fibrinolytic system in health and disease. This program will deal with the identification of abnormal plasminogens found in the plasmas of patients with thrombotic diseases. The variant plasminogens will be isolated and characterized by physical and chemical methods; the molecular defect, perhaps a single amino acid substitution, will be determined using classical protein chemistry methods. The plasminogen defect is present in the plasminogen gene itself and is produced by either a single base-pari change, or a larger structural change in the gene, and this defect is inherited in a Mendelian fashion. The plasminogen gene map and the plasminogen cDNA (clone) will be used in these studies.